Jamie (Catherine Keener) knocks on John’s door repeatedly, but there is no response except for the persistent bass beat of techno music. She uses her key to unlock the door and walks in on John (John C. Reilly) masturbating furiously. He’s caught off guard and tells her he had jock itch and asks what she’s doing here. Jamie left John 6 years ago, and his life has been in a rut ever since. She tells him that she is marrying her boyfriend, Tim (Matt Walsh). John is upset and tells her that he knew it, but Jamie tells him that it is time for him to move on. She tells him that he should come to a party with her and Tim but John resists.

At the party, Tim and Jamie try to get John out of his shell. He awkwardly hits on girls and fails terribly. Jamie tells him to be vulnerable but he takes that to the deep end and drives a young woman away by telling her he has accepted that he might die alone. He drinks more and gets smashed. He wanders into the garden and starts peeing the bushes when Molly (Marisa Tomei) walks by and says “nice penis.” John and Molly make small talk and John tells her he’s going to mess up, but Molly says he’s doing fine. John here’s his favorite song (Don’t You Want Me Baby by The Human League) and runs into the house. Molly follows him and witnesses John trying to start up a dance party but everyone just watches him dance. Molly joins him and sings along and soon Tim and Jamie are dancing too. Everyone has a good time. Molly and John go back to his house and have sex.

When John wakes up, he finds a note thanking him and telling him to call Molly later. He calls her and arranges for a date that night at his place. He spends the day cleaning his house and making dinner for Molly. Molly is impressed and John tells her that he likes her. She says that he life is complicated but that she is definitely interested. They have sex again and this time John catches her when she leaves. He asks if she’s married and she tells him no.

He follows her to her house that night but doesn’t see a husband. He passes out in his car and wakes up the next morning. He looks around Molly’s house until he awkwardly encounters Cyrus (Jonah Hill). Cyrus invites John in and shows him his music. Cyrus gives an entertaining performance and Molly starts dancing to it when she comes into the house. When she sees John she gets incredibly embarrassed and the three end up having an incredibly awkward dinner. Cyrus is 22 and he and his mom have a weird relationship in that they are like best friends instead of mother and son. Cyrus explains that his dad has never been in the picture and that Molly has never brought someone home before. John awkwardly tells Cyrus that he and Molly slept together and that he wants to treat Cyrus like an adult instead of a child. Molly is mortified but Cyrus thanks him, appreciating the honesty. Cyrus asks Molly if John will be staying the night.

John and Molly sleep together in the night but she insists that they keep the door open. The next morning, John can’t find his sneakers anywhere and sees Molly and Cyrus prepare for their daily hang out in Elysian Park. John walks to work without his sneakers and tells Jamie about the experience. He wants her insight onto what kind of people Molly and Cyrus are, so the next day they run through Elysian Park and “accidentally” run into them. The group hangs out and Molly and Cyrus wrestle, but aside from that nothing seems really weird. Jamie tells John that everything is fine.

That night, John comes over and Molly begins to seduce him. However, just as they are about to have sex, Cyrus starts screaming. Molly spends the night cuddling with him to keep him from being afraid of his night terrors. John goes to check on Molly in the middle of the night, but Cyrus is behind him and asks to talk. In the kitchen, Cyrus tells John that Molly thinks he’s coming on too strongly, but John is surprised at this. John leaves a note for Molly saying that he thought she and Cyrus needed some alone time. However, Cyrus takes the note and destroys it. He tells Molly that John wanted to slow things down and Molly is surprised. Cyrus pretends to be offended and bursts out of the house.

Molly doesn’t hear from him all day, so she calls John to comfort her. He spends a lot of time with her until Cyrus finally returns. He tells them that he feels he is butting in on their relationship and that it can’t properly flourish if he is present. He decides to move out and leaves to go paint his new room and asks Molly to pack up his stuff for tomorrow. Molly cries herself to sleep that night. Once she goes to work, John packs for Cyrus and finds his sneakers hidden in Cyrus’s closet. Realizing the implications of this, he coldly informs Cyrus that he packed up Cyrus’s things and sends him on his way.

Molly takes it very hard at first, but with John’s help they move past Cyrus’s departure. Eventually, John and Molly move in together. One night, after a date, the pair come home and start fooling around on the couch only to find Cyrus staring at them from the kitchen table. Cyrus tells Molly that he had a panic attack and that he wants to move back in. John, aware of Cyrus’s game, asks to speak with him alone; man to man. When John shows him the shoes, Cyrus reveals his malicious nature and John is happy that Cyrus is finally honest. The two declare war on each other but put on a show when Molly enters the room. Cyrus tells her he will bring his stuff back tomorrow but John tells him that he had to overcome his own anxieties at some point and did so in a similar manner. Cyrus brushes this off and moves back in.

John wants to tell Molly about Cyrus’s behavior. Jamie, who is trying to plan her wedding, tells John that he should just tell her and that if she cares, she will listen. John is afraid of going up against Cyrus because no matter what, Molly will always have him but John would be left alone again. However, John works up the courage to tell Molly about the shoe incident and admit that there might be something wrong with Cyrus (as Cyrus, outside of the room, shows John cardboard cut outs telling him that he’s going down).

The night before Jamie’s wedding, Molly tells John that Cyrus will be joining them. John is somewhat alarmed but takes it in stride. That night he goes to Cyrus’s room and asks him if he knows what it’s like to be punched in the face. Cyrus is confused but John makes himself clear: Jamie’s wedding is an important day for her and if Cyrus starts any shit to make John look bad in front of the guests, John will knock him out. The next morning Molly asks Cyrus if he knows how important this day is for John and gives him a knowing look.

At the wedding, Molly holds John’s hand while Tim and Jamie say their “I do”s. Cyrus sees this and gets alarmed. He spends the entire reception drinking large amounts of liquor until he is obliterated. He observes John and Molly happy in a corner and loses it. When John goes into the bathroom, Cyrus follows him and attacks him, screaming “You can’t fucking marry her, she’s all I have!” John is eventually tackled out of the bathroom and lands on the ground in front of everyone, but flips Cyrus over and starts shaking him. Molly yells at him to let Cyrus go as Cyrus says that John attacked him in the bathroom. John realizes that he has come off as the attacker to everyone in the party and decides to leave. He tells Molly to open her eyes and leaves her to tend to Cyrus.

After the wedding, Molly visits John. He tells her that they can’t work because since Day 1 Cyrus has been sabotaging their relationship. He tells her he doesn’t want to commit to end up alone again two years later and that even though he likes her, he fucking hates Cyrus. He moves out and into a dingy little one bedroom apartment.

Molly sits down and talks to Cyrus and apologizes for failing him as a mother. He protests but Molly tells him she knows about the shoes and what happened. Cyrus is left in a state of shock and Molly goes to bed. Over the next few weeks, we just see Molly in a despondent state. Cyrus realizes what he’s done and pays John a visit.

John does not take kindly to seeing Cyrus and refuses to open the door. He yells at Cyrus for 3 minutes about Cyrus having been such a bastard that he couldn’t let Molly be with anyone but him and that it was Cyrus’s fault John was living in this shithole. He eventually opens the door and sits next to Cyrus. They open up and Cyrus tells John that he needs to come back. John is reluctant, sensing a trap but Cyrus then (in earnest) asks how John beat his own anxiety attacks. John tells Cyrus that he lied about those since it was war and John wanted Cyrus gone. The two laugh over that and Cyrus has John bring him home. When Cyrus goes to get John’s stuff from the garage, he instead sends Molly out.

Molly and John look at each other from the street and John exits his car, ready to give their relationship another shot.